Transposon-sequencing across multiple Mycobacterium abscessus isolates reveals significant functional genomic diversity among strains
ABSTRACT Mycobacterium abscessus (Mab) is a clinically significant pathogen and a highly genetically diverse species due to its large accessory genome. The functional consequence of this diversity remains unknown mainly because, to date, functional genomic studies in Mab have been primarily performe...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2025-02-01
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| Series: | mBio |
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| Online Access: | https://journals.asm.org/doi/10.1128/mbio.03376-24 |
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| author | Chidiebere Akusobi Sanjeevani Choudhery Bouchra S. Benghomari Ian D. Wolf Shreya Singhvi Thomas R. Ioerger Eric J. Rubin |
| author_facet | Chidiebere Akusobi Sanjeevani Choudhery Bouchra S. Benghomari Ian D. Wolf Shreya Singhvi Thomas R. Ioerger Eric J. Rubin |
| author_sort | Chidiebere Akusobi |
| collection | DOAJ |
| description | ABSTRACT Mycobacterium abscessus (Mab) is a clinically significant pathogen and a highly genetically diverse species due to its large accessory genome. The functional consequence of this diversity remains unknown mainly because, to date, functional genomic studies in Mab have been primarily performed on reference strains. Given the growing public health threat of Mab infections, understanding the functional genomic differences among Mab clinical isolates can provide more insight into how its genetic diversity influences gene essentiality, clinically relevant phenotypes, and importantly, potential drug targets. To determine the functional genomic diversity among Mab strains, we conducted transposon-sequencing (TnSeq) on 21 genetically diverse clinical isolates, including 15 M. abscessus subsp. abscessus isolates and 6 M. abscessus subsp. massiliense isolates, cataloging all the essential and non-essential genes in each strain. Pan-genome analysis revealed a core set of 3,845 genes and a large accessory genome of 11,507. We identified 259 core essential genes across the 21 clinical isolates and 425 differentially required genes, representing ~10% of the Mab core genome. We also identified genes whose requirements were subspecies, lineage, and isolate-specific. Finally, by correlating TnSeq profiles, we identified 19 previously uncharacterized genetic networks in Mab. Altogether, we find that Mab clinical isolates are not only genetically diverse but functionally diverse as well.IMPORTANCEThis study investigates the genetic diversity of Mycobacterium abscessus (Mab), a bacteria known for causing difficult-to-treat infections. Researchers performed transposon-sequencing (TnSeq) on 21 different clinical isolates of Mab to identify essential and non-essential genes in each strain. Through this analysis, they identified core genes required for growth across all strains. Interestingly, they also identified genes whose requirement for growth or “essentiality” were subspecies, lineage, and isolate-specific. This study reveals that Mab’s genetic diversity translates into significant functional differences among clinical isolates. Insights from this paper lay essential groundwork for future studies exploring the biological and clinical implications of genetic diversity in Mab clinical isolates. Understanding this diversity could guide targeted therapies and offer new insights into managing infections caused by Mab, a growing public health concern. |
| format | Article |
| id | doaj-art-e131af5aecb64f46a9760d6df0abdca1 |
| institution | Kabale University |
| issn | 2150-7511 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj-art-e131af5aecb64f46a9760d6df0abdca12025-02-05T14:00:48ZengAmerican Society for MicrobiologymBio2150-75112025-02-0116210.1128/mbio.03376-24Transposon-sequencing across multiple Mycobacterium abscessus isolates reveals significant functional genomic diversity among strainsChidiebere Akusobi0Sanjeevani Choudhery1Bouchra S. Benghomari2Ian D. Wolf3Shreya Singhvi4Thomas R. Ioerger5Eric J. Rubin6Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USADepartment of Computer Science and Engineering, Texas A&M University, College Station, Texas, USADepartment of Biology, Northeastern University, Boston, Massachusetts, USADepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USADepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USADepartment of Computer Science and Engineering, Texas A&M University, College Station, Texas, USADepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USAABSTRACT Mycobacterium abscessus (Mab) is a clinically significant pathogen and a highly genetically diverse species due to its large accessory genome. The functional consequence of this diversity remains unknown mainly because, to date, functional genomic studies in Mab have been primarily performed on reference strains. Given the growing public health threat of Mab infections, understanding the functional genomic differences among Mab clinical isolates can provide more insight into how its genetic diversity influences gene essentiality, clinically relevant phenotypes, and importantly, potential drug targets. To determine the functional genomic diversity among Mab strains, we conducted transposon-sequencing (TnSeq) on 21 genetically diverse clinical isolates, including 15 M. abscessus subsp. abscessus isolates and 6 M. abscessus subsp. massiliense isolates, cataloging all the essential and non-essential genes in each strain. Pan-genome analysis revealed a core set of 3,845 genes and a large accessory genome of 11,507. We identified 259 core essential genes across the 21 clinical isolates and 425 differentially required genes, representing ~10% of the Mab core genome. We also identified genes whose requirements were subspecies, lineage, and isolate-specific. Finally, by correlating TnSeq profiles, we identified 19 previously uncharacterized genetic networks in Mab. Altogether, we find that Mab clinical isolates are not only genetically diverse but functionally diverse as well.IMPORTANCEThis study investigates the genetic diversity of Mycobacterium abscessus (Mab), a bacteria known for causing difficult-to-treat infections. Researchers performed transposon-sequencing (TnSeq) on 21 different clinical isolates of Mab to identify essential and non-essential genes in each strain. Through this analysis, they identified core genes required for growth across all strains. Interestingly, they also identified genes whose requirement for growth or “essentiality” were subspecies, lineage, and isolate-specific. This study reveals that Mab’s genetic diversity translates into significant functional differences among clinical isolates. Insights from this paper lay essential groundwork for future studies exploring the biological and clinical implications of genetic diversity in Mab clinical isolates. Understanding this diversity could guide targeted therapies and offer new insights into managing infections caused by Mab, a growing public health concern.https://journals.asm.org/doi/10.1128/mbio.03376-24Mycobacterium abscessusgenetic diversitytransposon-sequencingessential genesfunctional diversity |
| spellingShingle | Chidiebere Akusobi Sanjeevani Choudhery Bouchra S. Benghomari Ian D. Wolf Shreya Singhvi Thomas R. Ioerger Eric J. Rubin Transposon-sequencing across multiple Mycobacterium abscessus isolates reveals significant functional genomic diversity among strains mBio Mycobacterium abscessus genetic diversity transposon-sequencing essential genes functional diversity |
| title | Transposon-sequencing across multiple Mycobacterium abscessus isolates reveals significant functional genomic diversity among strains |
| title_full | Transposon-sequencing across multiple Mycobacterium abscessus isolates reveals significant functional genomic diversity among strains |
| title_fullStr | Transposon-sequencing across multiple Mycobacterium abscessus isolates reveals significant functional genomic diversity among strains |
| title_full_unstemmed | Transposon-sequencing across multiple Mycobacterium abscessus isolates reveals significant functional genomic diversity among strains |
| title_short | Transposon-sequencing across multiple Mycobacterium abscessus isolates reveals significant functional genomic diversity among strains |
| title_sort | transposon sequencing across multiple mycobacterium abscessus isolates reveals significant functional genomic diversity among strains |
| topic | Mycobacterium abscessus genetic diversity transposon-sequencing essential genes functional diversity |
| url | https://journals.asm.org/doi/10.1128/mbio.03376-24 |
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